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Biomedical subjects

S Hagiwara

Publications and source records attributed to S Hagiwara.

At least 73 records · Page 4Linked to original sources

Radiosurgery for acoustic neurinoma with rapid growth and relatively high staining indexes for proliferating cell nuclear antigen and MIB-1.

A 54-year-old female presented with a rapidly growing acoustic neurinoma. The tumor doubling time was 216 days or less before surgery and staining indexes for proliferating cell nuclear antigen (PCNA) and MIB-1 were relatively high (4.1% and 2.1%, respectively). The tumor was partially removed, but regrowth was detected with a tumor doubling time of 205 days. She underwent gamma knife radiosurgery for the residual tumor. The periphery of the tumor was irradiated with a dose of 15 Gy. Magnetic resonance imaging 30 months later demonstrated significant tumor shrinkage. The tumor half time following irradiation was determined to be 401 days. Neither surgery nor radiosurgery produced any additional neurological deficit or complications. Gamma knife radiosurgery can control neurinoma growth even when the tumor shows rapid growth and a relatively high growth fraction indicated by high staining indexes for PCNA or MIB-1.

Cranial Nerve Neoplasms↗

Gamma knife radiosurgery for brain tumors: postirradiation volume changes compared with preradiosurgical growth fractions.

The postradiosurgical volume changes were compared with preradiosurgical growth fractions defined as the tumor doubling time and/or MIB-1 staining index in 14 patients who underwent gamma knife radiosurgery for treatment of various brain tumors. The mean preradiosurgical observation period using neuroimaging techniques was 750 days (range 80-2967 days), and the mean follow-up period after radiosurgery was 664 days (range 328-1100 days). There were four neurinomas, three meningiomas, two craniopharyngiomas, two gliomas, one hemangioblastoma, one pituitary tumor, and one intracranially infiltrative lacrimal gland tumor. The mean patient age at the time of radiosurgery was 52 years (range 8-81 yrs). There were eight males and six females. Following gamma knife radiosurgery, the mean tumor half time was estimated to be 789 days (range 124-2101 days), and the volume reduction against the preradiosurgical tumor volume ranged from 6.3% to 76.1%. This study demonstrates that gamma knife radiosurgery can control tumor growth despite the lack of a correlation with preradiosurgical tumor growth or staining indices for MIB-1. Analyses of this type are essential to show that an "unchanged tumor volume" as demonstrated by postradiosurgery follow-up neuroimaging can be regarded as showing successful radiosurgery.

Adolescent↗

Perioperative antimicrobial prophylaxis in neurosurgery: clinical trial of systemic flomoxef administration and saline containing gentamicin for irrigation.

The efficacy of a new protocol consisting of a prophylactic antibiotic regimen of peri- and postoperative intravenous administration of flomoxef and irrigation of the operative field with saline containing gentamicin was assessed by comparing infection rates in two consecutive series of patients who underwent neurosurgical procedures. Group A received postoperative flomoxef administration, with saline containing no antibiotics for irrigation, from July 1988 to December 1989. Group B received the new protocol from January 1990 to December 1991. For further evaluation, this protocol was continued in most patients who underwent surgery from January 1992 through December 1993 (Group C). Only adult or adolescent patients who underwent clean neurosurgical procedures were included. The number of patients and procedures in each group were: 76 patients (97 procedures) in Group A, 103 (133) in Group B, and 107 (137) in Group C. There were no significant differences between Groups A and B in age, sex, clinical category, coexistent disease, clinical outcome, surgical procedures, general anesthesia, emergency operation, steroid administration, and the timing (season), duration, and frequency of surgery. Meningitis developed in three patients and subcutaneous infection in one in Group A. None of the patients in Group B experienced postoperative infection. This difference in infection rates (4.1% vs. 0%) was statistically significant (p = 0.0305). Furthermore, no postoperative infections developed in the Group C patients. The most appropriate interval for multiple dose administration was determined by analyzing intraoperative time-related changes in the serum flomoxef concentration during surgery in 21 recent patients. Serum flomoxef concentrations fell below therapeutic levels (3.0 micrograms/ml) by the 6th post-administration hour in 70% of patients. We conclude that this antibiotic regimen significantly reduces the postoperative infection rate following neurosurgical procedures. Multiple dose administration of flomoxef is recommended when the duration of surgery is 6 hours or more.

Adult↗

Monoclonal antibodies (NU-T1 and NU-T2) recognizing antigens expressed on human T cells.

Two murine monoclonal antibodies (mAb) designated as NU-T1 and NU-T2 were generated to identify the novel antigens expressed on human T cells. NU-T1 reacted with peripheral blood T cells, but not with granulocytes or monocytes, whereas NU-T2 were not reactive with peripheral blood lymphocytes, granulocytes or monocytes. Both NU-T1 and NU-T2 reacted with thymocytes. The incidence of NU-T1 or NU-T2 reactivity with the leukemic cells from patients with various types of leukemia was as follows: 12/12 or 4/12 in acute lymphocytic leukemia (ALL) of T cell type, 6/6 or 0/7 in adult T cell leukemia, 0/6 or 0/19 in ALL of non-T non-B cell type, and 0/8 or 0/8 in acute myelocytic leukemia, respectively. The incidence of NU-T1 and NU-T2 reactivity with human leukemic T cell lines were 4/10 and 5/10, respectively. In contrast, neither NU-T1 nor NU-T2 reacted with B cell lines, non-T non-B cell lines, or myeloid cell lines tested. These results indicate that NU-T1 and NU-T2 recognize two distinct differentiation antigens expressed on the cells in the T cell lineage. These mAb would be useful reagents to study the function of human T cells and the immunophenotyping of human T cell malignancies.

Antibodies, Monoclonal↗

[Hypersensitivity pneumonitis monitored with serum KL-6, a marker of interstitial pneumonia].

A 44-year-old man was hospitalized because of exertional dyspnea that had progressed for one month. A chest X-ray film showed bilateral small nodular and reticular shadows. The patient presented with a positive inflammatory reaction and hypoxemia. Bronchoalveolar davage fluid had a high lymphocyte fraction and a low CD4/CD8 ratio. Trichosporon cutaneum antibodies were detected, and a specimen obtained by transbronchial lung biopsy showed alveolitis with granuloma formation. The patient reacted positively on a provocation test that was done by having him stay home for 5 days. Summer-type hypersensitivity pneumonitis was diagnosed, and a steroid was administered because of the prolonged abnormal chest roentgenographic findings. KL-6, a mucinous high-molecular-weight glycoprotein that is expressed on Type II pneumonocytes, was retrospectively used as a marker of pneumonitis. A new kit for enzyme-linked immunoassay (ED046) was used to measure the serum KL-6 level. The serum KL-6 level peaked approximately 10 days after the patient was admitted to the hospital and was thus kept away from antigens, and also after the provocation test. The steroid treatment was started, the KL-6 level decreased gradually. Within 2 months after steroid treatment began, the dose of the steroid was reduced and the KL-6 level decreased below the upper limit of normal. The KL-6 level remained low thereafter; it was not influenced by liver dysfunction or other inflammatory processes. However, the C-reactive protein level decreased rapidly after provocation and thereafter immediately returned to almost zero. The lactate dehydrogenose level peaked 8 days after provocation and decreased rapidly after steroid treatment. These results suggest that the serum KL-6 level provides new information regarding the clinical course and treatment of interstitial pneumonia. In addition KL-6 may be useful form monitoring disease activity, especially while tapering the dose of steroids in patients with interstitial pneumonia.

Adult↗

[Successful treatment of acute non-lymphoblastic leukemia from myelodysplastic syndrome by combination of human macrophage colony-stimulating factor (M-CSF) and low dose cytosine arabinoside: M-CSF-induced proliferation and tyrosine phosphorylation in leukemic blasts].

An 84-year-old woman was admitted with acute non-lymphoblastic leukemia transformed from myelodysplastic syndrome. We examined the signal transduction of the leukemic blasts. Stimulation of the blasts by macrophage colony-stimulating factor (M-CSF) resulted in tyrosine phosphorylation of several cellular proteins. In vitro proliferation of leukemic blasts was stimulated by M-CSF, but not by granulocyte colony-stimulating factor. Based upon these findings, combined therapy with M-CSF and low dose cytosine arabinoside (ara-C) was successful. After her recovery, we confirmed marked reduction of blasts and disappearance of M-CSF-responsive cells. These results suggest that M-CSF could enhance the cytotoxic effect of ara-C on leukemic blasts via its intracellular signaling pathway linked to proliferation.

Aged↗

[Tonoko pneumoconiosis with deposition of titanium].

A 56-year-old man had worked as a furniture painter and had been exposed to tonoko polishing powder for 30 years. He had complained of dyspnea on exertion for 7 years, and was admitted to our hospital in 1991. A chest X-ray film revealed large opacities and emphysematous changes in both lung fields. Tonoko pneumoconiosis was diagnosed after transbronchial lung biopsy. Home oxygen therapy was given because of progressive hypoxemia, but the patient died of respiratory failure. At autopsy, examination of the lungs showed severe emphysematous changes, and collapse of alveoli. Many gray masses resembling coating cement were seen especially in the upper lobes. Microscopical examination showed that the large opacities were composed of hyaline nodules, similar to silicotic nodules, with anthracosis. Scanning electron microscopy with X-ray microanalysis revealed a high concentration of titanium in the gray mass. A low dose of titanium would not be expected to induce fibrotic changes in the lung, but a high dose and long-term exposure might have that effect. Titanium contained in paint might have exacerbated tonoko pneumoconiosis in this patient.

Dust↗

Transgenic expression of VpreB-3 under the control of the immunoglobulin heavy chain enhancer and SV40 promoter.

Recently we isolated a novel gene, VpreB-3 gene from the cDNA library of a pre-B cell clone. This gene is selectively expressed in pre-B and bone marrow-derived B cell lines. Its products are associated with the immunoglobulin heavy (IgH) chain in pre-B cell line. In the present study, to address the role of VpreB-3 on B cell development, transgenic mice carrying the VpreB-3 gene under the control of the IgH enhancer and SV40 promoter were produced. The transgenic mice expressed the VpreB-3 gene in bone marrow and spleen at a high level compared with control mice. In the thymus, the expression of the transgene was also detected, although its level was low. Flow cytometry analysis revealed that the frequency of CD45R+ and mu+ B cells were reduced in the bone marrow of 2 of the 11 transgenic mice and also reduced in the spleen of 1 of the transgenic mice. Furthermore, the results of a stromal cell-dependent B cell culture assay suggested that early B cell development, the differentiation from CD45R- B progenitor cells to CD45R+ pro-B cells, was delayed in the bone marrow cultures of 3 of the 5 transgenic mice compared with the control mice. These results suggested that VpreB-3 products may play some role in early B cell development at the stage of CD45R- B progenitor cells before the expression of surface mu chains.

Animals↗

[Pneumocystis carinii pneumonia associated with high levels of serum KL-6].

In May 1995, a 52-year-old man complaining of fever and dyspnea was admitted to a hospital. Based on clinical and radiographic findings, hypersensitivity pneumonitis was suspected. Steroid pulse therapy was unsuccessful, and he was then transferred to our hospital. A chest X-ray film showed bilateral ground-glass shadows and a high-resolution CT scan showed cystic air spaces. The number of CD4-positive lymphocytes in peripheral blood was very low. A test for anti-human immunodeficiency virus antibody was positive and Pneumocystic carinii was found in bronchoalveolar lavage fluid. The acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia were diagnosed. In this patient, the level of serum KL-6, a new marker of interstitial pneumonitis, was very high, and KL-6 was expressed on type II pneumocytes. The level of serum KL-6 may be useful as a marker of the activity of Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗

An inhibitory role for phosphatidylinositol 3-kinase in insulin secretion from pancreatic B cell line MIN6.

Phosphatidylinositol 3-kinase (PI3-kinase) has been implicated in the regulation of vesicular transport. We examined the roles of PI3-kinase in the glucose-induced insulin secretion from the pancreatic beta cell line MIN6 by using wortmannin, a potent inhibitor of PI3-kinase. Low concentrations of wortmannin markedly potentiated the glucose-induced insulin secretion. This effect was probably mediated by PI3-kinase inhibition. Furthermore, wortmannin completely canceled the suppressive effect of insulin-like growth factor-I on insulin secretion from MIN6 cells. On the basis of these results, we discuss a possible role of PI3-kinase in the negative feed-back regulation of insulin secretion.

Androstadienes↗

Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: a pilot study.

Fourteen patients with high-risk leukemia (six with relapsed AML, three with relapsed ALL, one with AML-M0, four with CML in myeloid blastic crisis) were treated with a combination chemotherapy of carboplatin (200-300 mg/m2/day) and cytosine arabinoside (100 mg/m2/day) by 24 h continuous infusion for 5-7 days. Five patients (35.7%) achieved complete remission including two patients complicated with myelofibrosis (one with AML-M0 and one with CML in myelo-megakaryocytic crisis). Thirteen patients had nausea and vomiting, five patients had severe, prolonged neutropenia for which it was necessary to administer granulocyte colony-stimulating factor and six patients had severe thrombocytopenia. We concluded that this regimen is effective for the treatment of high-risk leukemia.

Adolescent↗

Alterations of effector cell molecule expression on neutrophils in granulocyte colony-stimulating factor-producing tumour.

A 68-year-old man was diagnosed as having a granulocyte colony-stimulating factor (G-CSF)-producing mediastinal tumour. Mediastinotomy was performed, and thereafter the elevated leucocyte count and serum G-CSF concentration returned to the normal range. The surface expression of effector cell molecules on neutrophils was serially examined. Before operation, the expression of FcRI and CR1 was increased but the expression of FcRIII and L-selectin was reduced in the patient. The altered expression of these molecules returned to the normal levels after operation. These findings suggest that G-CSF produced by the tumour modulated neutrophil effector cell molecule expression in the patient.

Aged↗

Methicillin-resistant Staphylococcus aureus: colonization and development of infection in patients with haematological disorders.

A retrospective study of 53 patients with haematological disorders whose bacterial cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA), was performed to analyse the risk factors for MRSA infection, and the prognostic factors. Sixteen patients showed colonization by MRSA but never developed infection(C), 16 showed colonization and subsequent infection(C-I), while 21 had MRSA infection at the time of first culture (I). Poor performance status, thrombocytopenia, increased serum urea nitrogen and decreased serum cholinesterase were more prominent in (I) than (C) + (C-I). The risk factors associated with the development of infection from colonization were age and serum cholinesterase. In addition, lower respiratory tract infection as a type of infection, non-remission status of the haematological malignancy and an inappropriate antibiotic therapy were associated with a poor prognosis for MRSA infection.

Blood Urea Nitrogen↗

Growth rate of intracranial meningioma: tumor doubling time and proliferating cell nuclear antigen staining index.

The relationship between tumor doubling time, estimated by serial computed tomography (CT), and the proliferating cell nuclear antigen (PCNA) staining index of the tumor specimen was analyzed in 12 patients with nine partially or subtotally resected meningiomas and three meningiomas which recurred after gross total removal. There were nine meningothelial and three fibrous meningiomas. Malignant meningiomas and hemangiopericytomas were excluded. Serial CT was performed at various intervals ranging from 354 to 2007 days. Formalin-fixed, paraffin-embedded archival tissues were immunohistochemically stained using the avidin-biotin complex method with monoclonal antibody against PCNA. Percentages of PCNA-positive cells were calculated in 10 microscopic fields to determine the mean PCNA staining index. PCNA staining indexes varied from 0.13% to 7.46%. The tumor doubling time ranged from 197 to 7943 days and demonstrated a significant inverse rank correlation with the PCNA staining index (r = -0.89, p = 0.003). Meningiomas with PCNA staining indexes higher than 1% have comparatively short tumor doubling times of less than 5 years. PCNA immunostaining is a useful method for evaluating the proliferative activity of meningiomas.

Biomarkers, Tumor↗

Posterior cerebral artery aneurysm associated with unilateral internal carotid artery agenesis--Case report.

A 38-year-old housewife presented with a ruptured aneurysm associated with unilateral internal carotid artery agenesis. She had been in good health until May 31, 1994, when she was admitted to our facility immediately after sudden onset of headache and nausea. She was alert and exhibited no focal neurological deficit on admission. Cerebral angiography demonstrated an aneurysm arising from the junction of the horizontal segment of the right posterior cerebral artery and posterior communicating artery. The right internal carotid artery was totally absent. High resolution computed tomography demonstrated absence of the right carotid canal in the skull base. Neck clipping of the aneurysm was carried out through the right pterional approach on June 2. She returned home 52 days after the surgery with mild paresis of the left upper extremity and has since resumed household activities. Early surgery may be recommended in a patient with a ruptured aneurysm associated with agenesis of the internal carotid artery to prevent catastrophic rebleeding, if the initial insult is mild and subsequent vasospasm is unlikely to occur.

Adult↗

Impaired retinal artery blood flow in IDDM patients before clinical manifestations of diabetic retinopathy.

OBJECTIVE: To determine whether hemodynamic changes in retinal arteries precede clinical manifestations of diabetic retinopathy and to examine the effects of control of hyperglycemia on retinal artery blood flow. RESEARCH DESIGN AND METHODS: We assessed blood flow in bilateral central retinal arteries in 50 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 20 sex- and age-matched control subjects using duplex Doppler sonography. We determined the peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged velocity (TAV), resistance index (RI), and pulsatility index (PI). RESULTS: PSV, EDV, and TAV were significantly lower in IDDM patients than in control subjects (P < 0.05, P < 0.01, and P < 0.01, respectively). The RI was significantly higher in IDDM patients than in control subjects (P < 0.01) and was significantly correlated with plasma levels of glucose in IDDM patients (r = 0.0.310, P = 0.0248). Multiple regression analysis identified the plasma levels of glucose as a significant determination of RI in IDDM patients. After 14 days of intensive insulin therapy in 7 IDDM patients, the RI and plasma levels of glucose showed significant decreases (P = 0.018, P = 0.001, respectively). CONCLUSIONS: Our results showed that changes in retinal hemodynamics were present before the clinical detection of overt diabetic retinopathy and suggest that the presence of short-term hyperglycemia partly contributes to impaired retinal circulation.

Adolescent↗

[Subgingival distribution of periodontopathic bacteria in periodontic patients and susceptibility of these bacteria to minocycline-HCl].

The present study was carried out to examine the distribution of six periodontopathic bacteria in deep periodontal pockets and to reconfirm the effect of Periocline on these periodontopathic bacteria. Samples from sixty-two periodontal pockets were collected at pocket depths of over 4 mm in twenty-one periodontitis patients aged 43 to 75 years. After sampling, Periocline was applied topically to the selected pockets once a week for four weeks and reexamined. The detected rates of the periodontopathic bacteria were Capnocytophaga sputigena (37.1%), Prevotella intermedia (22.6%), Porphyromonas gingivalis (22.6%), Fusobacterium nucleatum (20.1%), Actinobacillus actinomycetemcomitans (9.7%) and Eikenella corrodens (4.8%). The distribution of the bacteria was compound because two or three bacterial species were found to coexist. In view of the MIC of minocycline-HCI for these bacteria, increase of most of the measured bacteria was suppressed by the concentration of drugs, including Periocline. However, clinical strains of P. i. were considered to have low susceptibility to minocycline-HCl. In view of the effect of topical application of drugs, no significant differences were found. From these results, it was suggested that Periocline contained effective concentration of minocycline-HCl.

Adult↗